Why is the certification process important?
The certification process ensures that the method in question is traceable to the recommended accuracy base. Being certified also facilitates Food and Drug Administration (FDA) clearance of diagnostic products. In addition, ongoing certification assures the end users that the product is validated at all times. Many clinical laboratories rely on the diagnostic manufacturers to maintain certified methods. For physicians to apply the clinical guidelines issued by the National Cholesterol Education Program (NCEP), individual laboratory measurements must be traceable to the recommended accuracy base.
What is involved in the certification process?
The participating manufacturer or clinical laboratory contacts a CRMLN member laboratory about its desire to be certified and to obtain the protocol. Please see Procedures for Certification of Manufacturers and Procedures for Certification of Clinical Laboratories for additional information.
Can more than one instrument system or model be certified with the same set of samples?
Yes. This is cost effective and highly desirable but requires coordination within the manufacturing facility (especially if the systems are located in different locations) and with the CRMLN member laboratory. Sample volume and turnaround time are important considerations with this approach.
How long will the certification process take from sending samples to receiving the certificate?
As long as the CRMLN member laboratory is aware that samples are arriving and can plan the analytical runs accordingly, the entire process usually takes less than eight weeks. The clinical laboratory certification should be completed within four weeks. However, this should be verified by the CRMLN network laboratory with whom you have chosen to perform the reference method analyses.
What are the certification criteria?
The criteria can be found here: Procedures for Certification of Manufacturers.
When does the certificate expire?
The certificate expires two years from the date the data analysis was performed by the CRMLN member laboratory.
Does the CRMLN have a protocol for recertification?
Yes. The protocol and further information can be found here: Total Cholesterol Recertification Protocol for Manufacturerspdf icon.
Can a clinical laboratory or manufacturer recertify before the previous certificate expires?
The list of certified manufacturers is updated periodically. To remain on the list, a manufacturer should anticipate when the certificate expires and plan to repeat the certification. If the certification is not complete, the manufacturer’s name will not appear on the monthly update.
Is the freshness limit of the samples truly critical?
Yes. One of the primary reasons the CRMLN was established is because freezing, lyophilization, and other processes result in matrix effects that lead to such samples behaving differently from fresh patient samples. The CRMLN protocol, which calls for analysis of fresh samples by the manufacturer’s test method, is designed to allow manufacturers to verify their calibration so they obtain the correct result for patient samples. For total cholesterol, the levels of cholesterol in freshly collected samples probably do not change for several days. However, some small studies and anecdotal information indicate that HDL cholesterol and LDL cholesterol change upon storage, so the freshness guidelines are critical (for both the test methods and for the reference methods). The CRMLN has devised a “Sample Stability Protocol” to assist manufacturers in evaluating the stability of frozen samples over time. A copy of the protocol is available on this website (link).
What is the best way to verify that my analytical system has low bias before embarking on a full certification effort?
The best way is to perform a comparison with a CRMLN laboratory using six to 10 fresh samples. Another way is to analyze National Institute of Standards and Technology (NIST) SRM 1951b (Lipids in Frozen Human Serum) that was prepared using NCCLS protocol C37-A to minimize matrix effects.
Should my laboratory send in standards or calibrators to be analyzed by the reference method first?
No. It is not recommended that you send your standards to be analyzed by the reference methods because of matrix differences between fresh samples and calibrators.
Can CDC send me samples with assigned values to check out my method first?
Yes. CDC may be able to provide samples that are reference value assigned with TC, TG and HDL depending on availability. These samples are intended to be used as trueness control. Please contact CDC at firstname.lastname@example.org for more detail. You may also contact CRMLN members for such samples.
If my laboratory has “out-of-control” runs during the certification period, or if the samples analyzed include “out-of-control” values, can I simply eliminate the unusual values if the runs do not include any certification samples i.e., as long as I have a total of 20 runs?
If you have “out-of-control” runs during the certification process, you should investigate the reasons for these deviations before you re-analyze certification samples (or collection of a new set, depending on the time lapse). “Out-of-control” runs should not be reported.
Can we perform more than one run on the same day if each test run includes separate calibration and controls?
Yes. CRMLN uses the NCCLS definition of “run” and requires that runs be separated by 2 hours.
Can we use more than one instrument of the same model during the CRMLN lab comparison process?
Yes. More than one instrument from the same model may be used as long as they have different serial numbers. In this way, manufacturers may increase the number of runs that can be accomplished within a time period. However, different models must perform all of the analyses and be certified separately.
My company manufactures point-of-care (POC) instruments that are factory-calibrated. Are we required to define our runs the same way as traditional clinical analyzers?
Yes. A run for POC instruments is defined as an analysis of two samples in duplicate every two hours.
What materials are used in the CDC standardization programs?
Reference materials used in the programs are prepared from pooled human serum according to the Clinical and Laboratory Standards Institute (CLSI)external icon guideline C37-A (Preparation and Validation of Commutable Frozen Human Serum Pools as Secondary Reference Materials for Cholesterol Measurement Procedures; Approved Guideline) (5, 6). Portions of the sterile, filtered serum are dispensed into glass vials, which are sealed then frozen at -70°C.
LSP reference materials are stored and maintained frozen at or below -70°C. (Storing and maintaining HDL-C materials at or below -70°C is critical.) All such materials are shipped to participating laboratories by air mail special delivery in special insulated containers with sufficient dry ice to last at least 48 hours in the case of domestic delivery. Additional dry ice is added, as permitted, for delivery to international participants. Upon arrival, the frozen reference material must immediately be transferred to a freezer for storage at -70°C.
Use of trade names is for identification only and does not constitute endorsement by the CDC or the U.S. Department of Health and Human Services.